Mild Alzheimer’s disease – additional opinion
Short Summary

78-year-old male was diagnosed with possible mild Alzheimer’s disease. Medical history suggests a condition running a slow but steadily deteriorating course characterized by apathy as well as by impairment of memory, word finding difficulties and reduced vocabulary, impaired ability to make calculation and handle finances and difficulties in managing house work and going outside unsupervised. An episode with characteristics of delirium in the past is described as well. The neuropsychological evaluation describes moderate dementia. The patients doctors believe that that he may profit from an anti-cholinesterasic therapy.

Patient's Questions
  1. Do you confirm the diagnosis?

  2. Would you recommend any further diagnostic tests?

  3. Do you agree with the efficacy of the anti-cholinesterasic therapy suggested? Are there any better therapeutic alternatives?

  4. Any experimental therapies available in Europe?
 
Medical Background

78 year old male.
Medical History & Clinical Information
The patient is a widower, living with a caretaker 24 hours a day.
In 2003, prostate cancer treated with a radical prostatectomy surgery and subsequent radiotherapy.
No other internal pathologies and/or relevant surgeries.
 
Case History:
The patient was evaluated at the Alzheimer’s Center in August 2006, and at that time he was diagnosed with a “possible mild Alzheimer’s disease”.
Re-evaluated in December 2007.
 
Cognitive and behavioral history
From the medical history information collected from the son, the cognitive-behavioral condition seems to have slightly but globally worsened compared with last year:
he is very repetitive, doesn't remember recent events, has difficulty finding objects, does not remember to take medications, doesn’t show up at appointments because he forgets them; he shows signs of confabulation (compensatory false recollections);
has maintained memories of his youth and remembers distant past more clearly;
his spontaneous language is fluent but characterized by frequent difficulties to find quickly the right words; uses a reduced vocabulary compared with the past and resorts to circumlocutions in an attempt to be more informative; has no difficulty reading and writing but has problems with calculations;
adequate use of common objects;
confuses at times the use of the telephone with that of the remote control; knows how to use electric shaver but doesn’t cook anymore;
recognizes familiar faces and doesn’t make mistakes in layering his clothes;
has difficulty in managing cash money and doesn’t handle any longer bank transactions;
he doesn’t go out by himself because he would get lost; he moves around comfortably in his own apartment;
he is disoriented in time;
hallucinations and delirious thoughts, present at the last visit, have disappeared.
From a behavioral perspective, the patient is slightly inert and apathetic. No sleep or eating abnormalities. Does not report sphincter incontinence.
 
Autonomy in daily functions
The patient is capable of taking care of himself but requires supervision in some basic daily activities (ex. going out, managing money, housework, etc.)
 
Brain CAT scan (December 2007)
No focal abnormalities with pathological characteristics in sub- and supratentorial structures.
Normal ventricular system.
Median structures in axis.
 
Neuropsychological evaluation (December 2007)
At an informal visit, the patient appears disoriented in time, space and autobiographical parameters. Spontaneous speech is characterized by fluent language, with normal prosody, sufficiently adequate and communicative; an occasional anomic aphasia is noted, no paraphasia or dysgrammatism; moderate deficit in the oral comprehension of the speech;
Informally: slight dysgraphia, some acalculia in simple written calculations with preservation of arithmetic rules.
 
On the Overall Dementia Assessment test the patient has obtained a score of 63.8/100, corrected for age and education level to 64.5/100; this score is in the medium range of cognitive pathology and indicates an actual decrease of 0.81 points per month.
The score, obtained at the evaluation session, converted through a formula developed by the Center, corresponds to a M.M.S.E. (Mini-Mental State Exam) score of 17/30 (estimated within a wide confidence band).
 
Conclusions:
On the basis of medical history and psychometric information, the patient is confirmed to be suffering with a moderate degree, chronic cognitive progressive impairment of a degenerative nature, which by exclusion, is nosographically ascribable to probable Alzheimer’s disease.
Provided that the requirements set forth in the ministerial protocol are met, we believe that the patient may profit from an anti-cholinesterasic central therapy received at the out-patient facility. The aim is to begin the administration of anti-cholinesterase drugs.

Expert's Opinion

The report doesn’t mention changes in mood or abnormalities in the physical and neurological examination.  Results of blood tests including CBS, sed. rate, liver and renal functions, thyroid, Vitamin B12 and methylmalonic acid level  to exclude reversible causes of dementia is not mention either.
 
The temporal course and the characteristics of the cognitive, behavioral and activities of daily living deficits suggest that the most likely diagnosis in this case is a dementia syndrome. Alzheimer’s disease is the most common form of dementia at this age, and is indeed the most likely diagnosis. Alzheimer’s disease is still mostly diagnosed on clinical basis by considering the cognitive characteristics and the temporal progression of the disease.
 
However, additional causes of dementia should be considered.
-       Lewy body dementia ( LBD) is a possibility: I would consider this possibility however only in case that extrapyramidal signs such as rigidity and gait difficulties are evident on the neurological examination as the clinical course which is presented is not consistent with LBD ( i.e. there is no mention of fluctuation during the day, falls or visual hallucinations).

-       Fronto temporal dementia (FTD) is also a possibility: The provided clinical characteristics however are not consistent with this diagnosis either. The age of onset of the dementia is late and there is no history of personality changes - a prominent feature of FTD.

-       Although there is no history of vascular risk factors (such as elevated blood pressure, diabetes or coagulation defects) vascular dementia and mixed dementia (Alzheimer’s disease and vascular brain disease) are possible diagnoses. 

Other, even rarer conditions can’t be completely ruled out as well.

A more accurate diagnosis can be established by adding to the work-up a brain MRI and performing a lumbar puncture to evaluate for chronic infections and neoplastic conditions and for measurement of Tau protein (which is usually moderately elevated in Alzheimer’s disease and markedly elevated in conditions such as Creutzfeld Jacob disease). 
 
Practically: Considering that the patient is running a slow and progressive deterioration and assuming that the neurological and physical examinations are normal my recommendations would be:
To perform a routine laboratory work-up and brain MRI and next consider indications for LP according to the results.
 
Regarding therapy:
The present working diagnosis is possible Alzheimer’s disease. In such cases therapy with acetyl choline-esterase inhibitors (Aricept, Exelon, Reminyl) is certainly indicated.
Following several months of therapy and according to the therapeutic response and adverse effects profile Memantine should be considered either as add-on or as alternative.
The patient should be screened for depression and if present medicated for this condition as well.
There are clinical trials for investigational treatments underway at multiple centers throughout Italy and Europe. 
I would suggest that you contact a University-level hospital and inquire about available ongoing clinical trials. I will be able to provide further information regarding a particular trial once considered.

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